Acyclic ionophores

The Ba ISE containing the acyclic membrane carrier nonylphenoxy-poly(ethylenoxy)ethanol described by Levins [123] opened new fields in ion-selective electrodes based on synthetic acyclic ionophores. Simon and coworkers synthesized several hundred substances [3] that can be used for ISEs to determine alkaline earth ions, primarily Ca [4], and also [190], etc. (for a review, see [133, 154]). A natural ionophore for calcium is the antibiotic,... 

An acyclic ionophore (14.10) for lithium cations forms a hexadentate lipophilic envelope around the ion in an octahedral arrangement. The selectivity factor for Li over Na" was 40, a figure exceeding anything previously attained. Given intravenously, it increased uptake of lithium by the rat brain (Shanzer, Samuel and Korenstein, 1983). 

Some characteristic features of PVC sodium electrodes based on the acyclic ionophore (20) and the cyclic bis-12-crown-4 with aliphatic bridging (21) are compared with those of a glass electrode in Table 3.14. 

Lithium glass electrodes such as LAS 15-25B are quite inadequate since Li,Na is 0.3. The research effort to realize a high performance lithium ISE has centred on the synthesis and evaluation of dozens of cyclic and acyclic ionophores (55-59). 

Figure 10 Naturally occurring cyclic and acyclic ionophores.

Wierenga and coworkers prepared acyclic ionophores with specificity for calcium. These ionophores consisted of furan or tetrahydrofuran ligands pendent from bicyclo[2.2.Ijheptane (16) or bicyclo[3.2.1]octane (17) systems (Fig. 6). 

Finally, Kirsch and Simon prepared two different, acyclic ionophores (, 19 Figure 7), studied the ion-selectivity, and determined the stability constants. They found high selectivity for alkaline-earth metals, with respect to alkali metal cations. 

Crown-4 (lithium ionophore V, 1,4,7,10-tetraoxacyclododecane) [294-93-9] M 176.2, m 17°. The distilled crude product had to be crystd from pentane at -20° to remove acyclic material. It is then dried over P2O5. [Acta Chem Scand 27 3395 1973.]... 

In this review, recent development of active transport of ions accross the liquid membranes using the synthetic ionophores such as crown ethers and other acyclic ligands, which selectively complex with cations based on the ion-dipole interaction, was surveyed,... 

Lee, S. S. Yoon, I. Park, K.-M. Jung, J. H. Lindoy, L. F. Nezhadali, A. Rounaghi, G. Competitive bulk membrane transport and solvent extraction of transition and post transition metal ions using mixed-donor acyclic ligands as ionophores. J. Chem. Soc.-Dalton Trans. 2002, 2180-2184. 

The question of carrier design was first addressed for the transport of inorganic cations. In fact, selective alkali cation transport was one of the initial objectives of our work on cryptates [1.26a, 6.4]. Natural acyclic and macrocyclic ligands (such as monensin, valinomycin, enniatin, nonactin, etc.) were found early on to act as selective ion carriers, ionophores and have been extensively studied, in particular in view of their antibiotic properties [1.21, 6.5]. The discovery of the cation binding properties of crown ethers and of cryptates led to active investigations of the ionophoretic properties of these synthetic compounds [2.3c, 6.1,6.2,6.4-6.13], The first step resides in the ability of these substances to lipophilize cations by complexation and to extract them into an organic or membrane phase [6.14, 6.15]. 

A polymeric stack of macrocycles has been synthesized [6.72] and a cyclodextrin-based model of a half-channel has been reported [6.73]. Channel-type conduction of Na+ ions has been reported for a tris-macrocyclic ligand [6.74]. A derivative of the acyclic polyether ionophore monensin forms lithium channels in vesicles [6.75a], which may be sealed by diammonium salts [6.75b]. 

Vogtle has suggested that synthetic ionophores be classified as follows (21) cor-onands are macromonocyclic compounds with any heteroatoms cryptands are bi- and polymacrocyclic ligands with any heteroatoms and podands are acyclic coronand and cryptand analogs. The term crown ether is reserved for coronands with only oxygens as heteroatoms. Such a classification will be used hereafter. 

Wakita R, Matsumoto M, Nakatsuji Y, and Okahara M. Selective transport of lithium ions by an acyclic carboxylic ionophore with a quinaldate moiety through a bulk liquid membrane. J Mem Sci, 1991 57(2-3) 297-306. 

A quantitative 1,4-chirality transfer is observed in the construction of the acyclic segment C-l to C-ll 11 of the antibiotic ionophore A-23187 (12, calcimycin)441. Both the wanted and unwanted stereoisomer 9 and 10, obtained from the alcohol 8 by pyridinium chlorochromate oxidation followed by Grignard reaction with vinylmagnesium bromide, can be rearranged by the ester enolate procedure simply by changing the reaction conditions to give the stereoisomer 11 with the correct configuration at C-10. 

Because of their complex chemical structures and significant biological properties, polyether ionophore antibiotics have stimulated intensive studies of their total synthesis, which primarily require new synthetic methodologies for the control of stereochemistry in acyclic systems two excellent reviews covered the results until 1981 [1]. However, since then, only a few total syntheses have been achieved, because the extremely complex structures of the polyethers have required formidable efforts for synthesis, and much attention has focussed on efficient and stereoselective synthesis of the molecular framework of substituted tetrahydrofurans and tetrahydropyrans and spiroketal systems [2]. This review deals with the total synthesis of three representative complex polyethers, okadaic acid (1), antibiotic X-206 (2), and salinomycin (3) mainly focussing on the latter half of their synthesis. 

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